Background Cancer stem cells have been investigated as new targets for colorectal cancer (CRC) treatment. We recently reported that CD133+ colon cancer cells showed chemoresistance to 5-fluorouracil through increased survivin expression and proposed the survivin inhibitor YM155 as an effective therapy for colon cancer in an in vitro study. Here, we investigate the relationship between survivin and CD133 expression in surgically resected CRC to identify whether the results obtained in our in vitro study are applicable to clinical samples.
Methods We performed immunohistochemical staining for survivin and CD133 in surgically resected tissue from 187 stage II or III CRC patients. We also comparatively analyzed apoptosis according to survivin and CD133 expression using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling.
Results The results of the Mantel-Haenszel test established a linear association between nuclear survivin and CD133 expression (p = .018), although neither had prognostic significance, according to immunohistochemical expression level. No correlation was found between survivin expression and the following pathological parameters: invasion depth, lymph node metastasis, or histologic differentiation (p > .05). The mean apoptotic index in survivin+ and CD133+ tumors was higher than that in negative tumors: 5.116 ± 4.894 in survivin+ versus 4.103 ± 3.691 in survivin– (p = .044); 5.165 ± 4.961 in CD133+ versus 4.231 ± 3.812 in CD133– (p = .034).
Conclusions As observed in our in vitro study, survivin expression is significantly related to CD133 expression. Survivin may be considered as a new therapeutic target for chemoresistant CRC.
Citations
Citations to this article as recorded by
Upregulation of EMR1 (ADGRE1) by Tumor-Associated Macrophages Promotes Colon Cancer Progression by Activating the JAK2/STAT1,3 Signaling Pathway in Tumor Cells Rokeya Akter, Rackhyun Park, Soo Kyung Lee, Eun ju Han, Kyu-Sang Park, Junsoo Park, Mee-Yon Cho International Journal of Molecular Sciences.2024; 25(8): 4388. CrossRef
Antiapoptotic Gene Genotype and Allele Variations and the Risk of Lymphoma Osama M. Al-Amer, Rashid Mir, Abdullah Hamadi, Mohammed I. Alasseiri, Malik A. Altayar, Waseem AlZamzami, Mamdoh Moawadh, Sael Alatawi, Hanan A. Niaz, Atif Abdulwahab A. Oyouni, Othman R. Alzahrani, Hanan E. Alatwi, Aishah E. Albalawi, Khalaf F. Alsharif, Cancers.2023; 15(4): 1012. CrossRef
The Prognostic and Therapeutic Implications of the Chemoresistance Gene BIRC5 in Triple-Negative Breast Cancer Getinet M. Adinew, Samia Messeha, Equar Taka, Karam F. A. Soliman Cancers.2022; 14(21): 5180. CrossRef
EMR1/ADGRE1 Expression in Cancer Cells Upregulated by Tumor-Associated Macrophages Is Related to Poor Prognosis in Colorectal Cancer Rokeya Akter, Kwangmin Kim, Hye Youn Kwon, Youngwan Kim, Young Woo Eom, Hye-mi Cho, Mee-Yon Cho Biomedicines.2022; 10(12): 3121. CrossRef
Prognostic Significance of BIRC5/Survivin in Breast Cancer: Results from Three Independent Cohorts Nina Oparina, Malin C. Erlandsson, Anna Fäldt Beding, Toshima Parris, Khalil Helou, Per Karlsson, Zakaria Einbeigi, Maria I. Bokarewa Cancers.2021; 13(9): 2209. CrossRef
Obatoclax, a Pan-BCL-2 Inhibitor, Downregulates Survivin to Induce Apoptosis in Human Colorectal Carcinoma Cells Via Suppressing WNT/β-catenin Signaling Chi-Hung R. Or, Chiao-Wen Huang, Ching-Chin Chang, You-Chen Lai, Yi-Ju Chen, Chia-Che Chang International Journal of Molecular Sciences.2020; 21(5): 1773. CrossRef
M1 Macrophages Promote TRAIL Expression in Adipose Tissue-Derived Stem Cells, Which Suppresses Colitis-Associated Colon Cancer by Increasing Apoptosis of CD133+ Cancer Stem Cells and Decreasing M2 Macrophage Population Young Woo Eom, Rokeya Akter, Wanlu Li, Suji Lee, Soonjae Hwang, Jiye Kim, Mee-Yon Cho International Journal of Molecular Sciences.2020; 21(11): 3887. CrossRef
Emerging Importance of Survivin in Stem Cells and Cancer: the Development of New Cancer Therapeutics Neerada Meenakshi Warrier, Prasoon Agarwal, Praveen Kumar Stem Cell Reviews and Reports.2020; 16(5): 828. CrossRef
MMR-proficient and MMR-deficient colorectal cancer cells: 5-Fluorouracil treatment response and correlation to CD133 and MGMT expression Jaime A. Oliver, Raúl Ortiz, Cristina Jiménez-Luna, Laura Cabeza, Gloria Perazzoli, Octavio Caba, Cristina Mesas, Consolación Melguizo, Jose Prados Journal of Biosciences.2020;[Epub] CrossRef
Survivin rs9904341 polymorphism significantly increased the risk of cancer: evidence from an updated meta-analysis of case–control studies Abdolkarim Moazeni-Roodi, Saeid Ghavami, Mohammad Hashemi International Journal of Clinical Oncology.2019; 24(4): 335. CrossRef
CRISPR-Cas9 mediated CD133 knockout inhibits colon cancer invasion through reduced epithelial-mesenchymal transition Wanlu Li, Mee-Yon Cho, Suji Lee, Mirae Jang, Junsoo Park, Rackhyun Park, Aamir Ahmad PLOS ONE.2019; 14(8): e0220860. CrossRef
Diagnostic Approaches for Salivary Gland Tumors with Secretory and Microcystic Features Ha Young Woo, Eun Chang Choi, Sun Och Yoon Head and Neck Pathology.2018; 12(2): 237. CrossRef
MUC1‐ and Survivin‐based DNA Vaccine Combining Immunoadjuvants CpG and interleukin‐2 in a Bicistronic Expression Plasmid Generates Specific Immune Responses and Antitumour Effects in a Murine Colorectal Carcinoma Model C. Liu, Y. Xie, B. Sun, F. Geng, F. Zhang, Q. Guo, H. Wu, B. Yu, J. Wu, X. Yu, W. Kong, H. Zhang Scandinavian Journal of Immunology.2018; 87(2): 63. CrossRef
Activated STAT3 may participate in tumor progression through increasing CD133/survivin expression in early stage of colon cancer Wanlu Li, Mi-Ra Lee, Taeyeong Kim, Young Wan Kim, Mee-Yon Cho Biochemical and Biophysical Research Communications.2018; 497(1): 354. CrossRef
MiRNA-142-3p increases radiosensitivity in human umbilical cord blood mononuclear cells by inhibiting the expression of CD133 Fang Yuan, Lu Liu, Yonghong Lei, Yi Hu Scientific Reports.2018;[Epub] CrossRef
MLH1 enhances the sensitivity of human endometrial carcinoma cells to cisplatin by activating the MLH1/c-Abl apoptosis signaling pathway Yue Li, Shihong Zhang, Yuanjian Wang, Jin Peng, Fang Fang, Xingsheng Yang BMC Cancer.2018;[Epub] CrossRef
Establishment of CMab-43, a Sensitive and Specific Anti-CD133 Monoclonal Antibody, for Immunohistochemistry Shunsuke Itai, Yuki Fujii, Takuro Nakamura, Yao-Wen Chang, Miyuki Yanaka, Noriko Saidoh, Saori Handa, Hiroyoshi Suzuki, Hiroyuki Harada, Shinji Yamada, Mika K. Kaneko, Yukinari Kato Monoclonal Antibodies in Immunodiagnosis and Immunotherapy.2017; 36(5): 231. CrossRef